Role of adenosine in the regulation of coronary blood flow in swine at rest and during treadmill exercise

A pivotal role for adenosine in the regulation of coronary blood flow is still controversial. Consequently, we investigated its role in the regulation of coronary vasomotor tone in swine at rest and during graded treadmill exercise. During exercise, myocardial O2 consumption increased from 167 +/- 18 micromol/min at rest to 399 +/- 27 micromol/min at 5 km/h (P </= 0.05), which was paralleled by an increase in O2 delivery, so that myocardial O2 extraction (76 +/- 1 and 78 +/- 1% at rest and 5 km/h, respectively) and coronary venous PO2 (24.5 +/- 1.0 and 22.8 +/- 0.3 mmHg at rest and 5 km/h, respectively) remained unchanged. After adenosine receptor blockade with 8-phenyltheophylline (5 mg/kg iv), the relation between myocardial O2 consumption and coronary vascular resistance was shifted toward higher resistance, whereas myocardial O2 extraction rose to 81 +/- 1 and 83 +/- 1% at rest and 5 km/h and coronary venous PO2 fell to 19.2 +/- 0.8 and 18.9 +/- 0.8 mmHg at rest and 5 km/h, respectively (all P </= 0.05). Thus, although adenosine is not mandatory for the exercise-induced coronary vasodilation, it exerts a vasodilator influence on the coronary resistance vessels in swine at rest and during exercise

Coronary microvascular disease: the next frontier for Cardiovascular Research

No abstract available

Animal models of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50% of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models

Role of K(ATP)(+) channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine

The role of ATP-sensitive K(+) (K(ATP)(+)) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the contribution of K(ATP)(+) channels to vasomotor tone regulation in the systemic, pulmonary, and coronary vascular bed in nine treadmill-exercising swine. Exercise up to 85% of maximum heart rat